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PDBsum entry 3emh
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Gene regulation PDB id
3emh

 

 

 

 

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Contents
Protein chain
300 a.a. *
Ligands
ALA-ARG-ALA-GLU-
VAL-HIS
SO4 ×2
Waters ×267
* Residue conservation analysis
PDB id:
3emh
Name: Gene regulation
Title: Structural basis of wdr5-mll interaction
Structure: Wd repeat-containing protein 5. Chain: a. Fragment: unp residues 25-334. Synonym: bmp2-induced 3-kb gene protein. Engineered: yes. Mixed-lineage leukemia protein 1. Chain: b. Fragment: unp residues 2675-2687. Synonym: mll1.
Source: Homo sapiens. Organism_taxid: 9606. Gene: wdr5, big3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide following the sequence position 2675-2687 of uniprot entry q59ff2 (q59ff2_human)
Resolution:
1.37Å     R-factor:   0.190     R-free:   0.200
Authors: J.J.Song,R.E.Kingston
Key ref:
J.J.Song and R.E.Kingston (2008). WDR5 Interacts with Mixed Lineage Leukemia (MLL) Protein via the Histone H3-binding Pocket. J Biol Chem, 283, 35258-35264. PubMed id: 18840606 DOI: 10.1074/jbc.M806900200
Date:
24-Sep-08     Release date:   07-Oct-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61964  (WDR5_HUMAN) -  WD repeat-containing protein 5 from Homo sapiens
Seq:
Struc: 		334 a.a.
300 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M806900200 J Biol Chem 283:35258-35264 (2008)
PubMed id: 18840606  
 
 
WDR5 Interacts with Mixed Lineage Leukemia (MLL) Protein via the Histone H3-binding Pocket.
J.J.Song, R.E.Kingston.
 
  ABSTRACT  
 
WDR5 is a component of the mixed lineage leukemia (MLL) complex, which methylates lysine 4 of histone H3, and was identified as a methylated Lys-4 histone H3-binding protein. Here, we present a crystal structure of WDR5 bound to an MLL peptide. Surprisingly, we find that WDR5 utilizes the same pocket shown to bind histone H3 for this MLL interaction. Furthermore, the WDR5-MLL interaction is disrupted preferentially by mono- and di-methylated Lys-4 histone H3 over unmodified and tri-methylated Lys-4 histone H3. These data implicate a delicate interplay between the effector, WDR5, the catalytic subunit, MLL, and the substrate, histone H3, of the MLL complex. We suggest that the activity of the MLL complex might be regulated through this interplay.
 
  Selected figure(s)  
 
Figure 1.
MLL1 interacts with WDR5 through a histone H3-like motif. A, a series of deletion mutants of MLL1 was generated and tested for binding ability to WDR5 by gel filtration chromatography. MLL205 is the minimal construct that interacts with WDR5. B, the sequence in MLL1 required for WDR5 interaction contains a histone H3-like motif and is modestly conserved among MLLs. C, the histone H3-like motif in MLL1 was tested for binding to WDR5. The histone H3-like motif in MLL1 is sufficient to interact with WDR5. D, the histone H3-like motifs in MLL1, MLL2, MLL3, and MLL4 were tested for binding to WDR5 with GST pull-down experiments. Only MLL1 and MLL4 are able to bind WDR5. 		Figure 2.
Crystal structure of WDR5 bound to MLL1 peptide. A, top and side views of WDR5 bound to MLL1 peptide. The MLL1 peptide is bound to a pocket located at the center of WD40 β-propeller structure, previously shown to be a histone H3-binding pocket. B, F[o]-F[c] map (shown in 3σ) between a refined free WDR5 and data collected from the WDR5-MLLpeptide complex. C, superimposition between WDR5-MLL peptide (blue-green) and WDR5-H3 (yellow-red) complex structures. D, the electrostatic surface potential representations of WDR5-MLL1pep and WDR5-H3K4me2 complex structures. MLL1 peptide and H3K4me2 peptide utilize distinct pockets for binding.
 
  The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2008, 283, 35258-35264) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22231400 V.Migliori, J.Müller, S.Phalke, D.Low, M.Bezzi, W.C.Mok, S.K.Sahu, J.Gunaratne, P.Capasso, C.Bassi, V.Cecatiello, A.De Marco, W.Blackstock, V.Kuznetsov, B.Amati, M.Mapelli, and E.Guccione (2012).
Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance.
  Nat Struct Mol Biol, 19, 136-144.
PDB code: 4a7j
22437499 W.C.Chao, K.Kulkarni, Z.Zhang, E.H.Kong, and D.Barford (2012).
Structure of the mitotic checkpoint complex.
  Nature, 484, 208-213.
PDB code: 4aez
21468892 C.Xu, and J.Min (2011).
Structure and function of WD40 domain proteins.
  Protein Cell, 2, 202-214.
PDB codes: 3e0c 3fm0 3i2n 3ow8
21455483 T.Li, and W.G.Kelly (2011).
A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line.
  PLoS Genet, 7, e1001349.  
21220120 V.Avdic, P.Zhang, S.Lanouette, A.Groulx, V.Tremblay, J.Brunzelle, and J.F.Couture (2011).
Structural and biochemical insights into MLL1 core complex assembly.
  Structure, 19, 101-108.
PDB code: 3p4f
21046623 A.Tuukkanen, B.Huang, A.Henschel, F.Stewart, and M.Schroeder (2010).
Structural modeling of histone methyltransferase complex Set1C from Saccharomyces cerevisiae using constraint-based docking.
  Proteomics, 10, 4186-4195.  
20451393 C.U.Stirnimann, E.Petsalaki, R.B.Russell, and C.W.Müller (2010).
WD40 proteins propel cellular networks.
  Trends Biochem Sci, 35, 565-574.  
20974918 C.Xu, C.Bian, W.Yang, M.Galka, H.Ouyang, C.Chen, W.Qiu, H.Liu, A.E.Jones, F.MacKenzie, P.Pan, S.S.Li, H.Wang, and J.Min (2010).
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).
  Proc Natl Acad Sci U S A, 107, 19266-19271.
PDB codes: 3jpx 3jzg 3jzh 3jzn 3k26 3k27
21124902 F.Cao, Y.Chen, T.Cierpicki, Y.Liu, V.Basrur, M.Lei, and Y.Dou (2010).
An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain.
  PLoS One, 5, e14102.  
20347844 J.R.England, J.Huang, M.J.Jennings, R.D.Makde, and S.Tan (2010).
RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
  J Mol Biol, 398, 518-529.  
20923397 K.L.Yap, and M.M.Zhou (2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
  Crit Rev Biochem Mol Biol, 45, 488-505.  
20236310 M.S.Cosgrove, and A.Patel (2010).
Mixed lineage leukemia: a structure-function perspective of the MLL1 protein.
  FEBS J, 277, 1832-1842.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
20433758 T.G.Natarajan, B.V.Kallakury, C.E.Sheehan, M.B.Bartlett, N.Ganesan, A.Preet, J.S.Ross, and K.T.Fitzgerald (2010).
Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon.
  Cancer Cell Int, 10, 13.  
20005892 Y.H.Takahashi, and A.Shilatifard (2010).
Structural basis for H3K4 trimethylation by yeast Set1/COMPASS.
  Adv Enzyme Regul, 50, 104-110.  
19556245 A.Patel, V.Dharmarajan, V.E.Vought, and M.S.Cosgrove (2009).
On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex.
  J Biol Chem, 284, 24242-24256.  
19852741 C.Bach, and R.K.Slany (2009).
Molecular pathology of mixed-lineage leukemia.
  Future Oncol, 5, 1271-1281.  
19578375 R.C.Trievel, and A.Shilatifard (2009).
WDR5, a complexed protein.
  Nat Struct Mol Biol, 16, 678-680.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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